CircularRNA CirCHIPK3promotes cell proliferation and invasion of breast cancer by spongingmiR-193a/HMGB1/PI3K/AKTaxis
CircularRNA CirCHIPK3promotes cell proliferation and invasion of breast cancer by spongingmiR-193a/HMGB1/PI3K/AKTaxis
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DOI：
10.1111/1759-7714.13603
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发表时间：
2020-08-06
期刊：
影响因子：
2.9
通讯作者：
Wang, Guang-Shun
中科院分区：
文献类型：
--
作者：
Chen, Zhen-Gang;Zhao, Hong-Jie;Wang, Guang-Shun
本研究旨在探讨环状RNA（circRNA）CirCHIPK 3在乳腺癌恶性增殖和转移中的作用机制。方法收集50例乳腺癌患者癌组织及癌旁组织，检测CirCHIPK 3的表达情况，分析其与乳腺癌预后的关系。本研究通过一系列体外和体内功能实验来阐明CirCHIPK 3在BC进展中的作用及其潜在的分子机制。此外，使用生物信息学、FISH、RIP、RNA下拉和荧光素酶报告基因测定来检查CirCHIPK 3、miR-193 a和HMGB 1的相互作用。进行蛋白质印迹分析以检查si-CirCHIPK 3转染后HMGB 1、p-PI 3 K、总PI 3 K、p-AKT和AKT的表达。结果CirCHIPK 3在BC中表达上调，提示BC患者预后较差。此外，发现CirCHIPK 3通过调节miR-193 a/HMGB 1/PI 3 K/AKT信号通路促进BC中的细胞增殖、迁移和侵袭。CirCHIPK 3充当miR-193 a的海绵以促进HMGB 1表达。si-CirCHIPK 3还抑制裸鼠中BC的肿瘤生长。si-CircCHIPK 3降低MDA-MB-231细胞中HMGB 1/PI 3 K/AKT信号的表达，而过表达CircCHIPK 3增强HMGB 1/PI 3 K/AKT信号。结论CirCHIPK 3调控miR-193 a/HMGB 1/PI 3 K/AKT信号通路，促进BC的发生发展，为BC的治疗提供了新的靶点。
Background The aim of this study was to explore the potential mechanism of circular RNA (circRNA) CirCHIPK3 on the malignant proliferation and metastasis of breast cancer (BC). Methods Human BC samples and their matched normal adjacent tissues were obtained from 50 patients to assess the expression of CirCHIPK3 and its relationship with BC prognosis. A series of in vitro and in vivo functional experiments were carried out to elucidate the role of CirCHIPK3 in BC progression and its underlying molecular mechanisms. Moreover, the interaction of CirCHIPK3, miR-193a, and HMGB1 was examined using bioinformatics, FISH, RIP, RNA-pull down and luciferase reporter assays. Western blot analysis was performed to examine the expression of HMGB1, p-PI3K, total PI3K, p-AKT, and AKT after si-CirCHIPK3 transfection. Results Upregulation of CirCHIPK3 was identified in BC, which predicted a worse prognosis in BC patients. Furthermore, it was found that CirCHIPK3 facilitated cell proliferation, migration, and invasion in BC by regulating miR-193a/HMGB1/PI3K/AKT signaling. CirCHIPK3 acted as a sponge for miR-193a to facilitate HMGB1 expression. si-CirCHIPK3 also inhibited tumor growth of BC in nude mice. si-CircCHIPK3 decreased HMGB1/PI3K/AKT signal expression in MDA-MB-231 cells, whereas overexpression of CircCHIPK3 enhanced HMGB1/PI3K/AKT signal. Conclusions CirCHIPK3 regulated miR-193a/HMGB1/PI3K/AKT signaling to facilitate BC development and progression, providing a novel therapeutic target for BC.